The coagulation of human blood is vitally dependent on the circulating blood platelet. Platelets adhere to tissue at the injury site (adhesion); they become sticky and clump to help plug the wound (aggregation); and they consolidate the clot by pulling in fibrin strands and squeezing out excess liquid (clot retraction). All three platelet functions are dependent on the platelet membrane interacting with another macromolecule(s). The objective of the proposed research is to understand the nature of the platelet membrane-fibrin interaction necessary for clot retraction. Techniques will be developed, utilizing immunologic methods, to locate the sites within fibrin that are in contact with the platelet membrane (contact peptides). Studies will also be made to verify the existence of a specific fibrin interaction site (receptor) in or on the platelet membrane. If successful, attempts will be made to isolate such a membrane receptor. The detailed molecular events involved in the macromolecular interaction will be studied by studying the isolated contact peptides. Analog peptides will be produced by peptide synthesis procedures and binding and conformational studies will serve to evaluate which amino acids are necessary for the interaction. In addition the relative importance of each contact peptide to the total binding free energy can be evaluated. This approach could be applied to studying platelet aggregation or adhesion or any other macromolecular association.